Chemogenetic stimulation of tonic locus coeruleus activity strengthens the default mode network
E. Oyarzabal, Li-Ming Hsu, Manasmita Das, T. Chao, Jingheng Zhou, Shengdeng Song, Weiting Zhang, Kathleen G. Smith, Natale R. Sciolino, Irina Y Evsyukova, Hong Yuan, Sung-Ho Lee, Guohong Cui, Patricia Jensen, Y. Shih
Science Advances April 1, 2022 DOI: 10.1126/sciadv.abm9898 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | chemogenetic activation of LC-NE neurons |
| Topics | Default mode network |
| Key findings | Chemogenetic activation of LC-NE neurons alters the coupling between neuronal activity and cerebral blood volume in the frontal default mode network and strengthens functional connectivity within that network. |
Abstract
The default mode network (DMN) of the brain is functionally associated with a wide range of behaviors. In this study, we used functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and spectral fiber photometry to investigate the selective neuromodulatory effect of norepinephrine (NE)–releasing noradrenergic neurons in the locus coeruleus (LC) on the mouse DMN. Chemogenetic-induced tonic LC activity decreased cerebral blood volume (CBV) and glucose uptake and increased synchronous low-frequency fMRI activity within the frontal cortices of the DMN. Fiber photometry results corroborated these findings, showing that LC-NE activation induced NE release, enhanced calcium-weighted neuronal spiking, and reduced CBV in the anterior cingulate cortex. These data suggest that LC-NE alters conventional coupling between neuronal activity and CBV in the frontal DMN. We also demonstrated that chemogenetic activation of LC-NE neurons strengthened functional connectivity within the frontal DMN, and this effect was causally mediated by reduced modulatory inputs from retrosplenial and hippocampal regions to the association cortices of the DMN.
Comparable studies
Other preclinical and animal studies on default mode network, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rat brains also have a default mode network Rats | 2012 | Observational study | |
| Large-scale topology and the default mode network in the mouse connectome Mouse brain | 2014 | Observational study | |
| Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network Anesthetized monkeys | 2016 | Observational study | |
| Psilocybin-induced default mode network hypoconnectivity is blunted in alcohol-dependent rats Healthy rats and a rat model of alcohol relapse | 2023 | Randomized, placebo-controlled crossover pharmaco-fMRI study | |
| Altered functional connectivity within the default mode network in two animal models with opposing episodic memories Rats (control, LPS-challenged, and footshock-exposed groups) | 2018 | Animal model study |
Citations in the library
Cited by 5
- Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance. Neuron February 5, 2025
- Space wandering in the rodent default mode network. bioRxiv September 1, 2023
- Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network. Nature Communications February 16, 2023
- Neuronal dynamics of the default mode network and anterior insular cortex: Intrinsic properties and modulation by salient stimuli. Science Advances February 15, 2023
- Brain-heart interactions in the neurobiology of consciousness Current Research in Neurobiology August 1, 2022
Cites 6
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
- Rat brains also have a default mode network Proceedings of the National Academy of Sciences February 21, 2012
- Large-scale topology and the default mode network in the mouse connectome Proceedings of the National Academy of Sciences December 15, 2014
- Unique spatiotemporal fMRI dynamics in the awake mouse brain. Current Biology February 7, 2022
- Regional, Layer, and Cell-Type-Specific Connectivity of the Mouse Default Mode Network Neuron December 1, 2020
and 1 more in the library